The intracellular pathogen Salmonella translocates a number of proteins, termed effectors, into the host cell to affect host cell processes and establish a safe replicative niche. Translocation is mediated by two Type Three Secretion Sytems (TTSS), which are encoded on Salmonella Pathogenicity Islands SPI1 and SPI2. The SPI2-encoded TTSS is induced intracellularly and is required for intracellular survival and replication and biogenesis of the Salmonella-containing vacuole (SCV). We have identified two SPI2 effectors, PipB and PipB2, that share some sequence similarity, primarily limited to their C-termini which are composed of tandem pentapeptide repeat domains. Both effectors are translocated by bacteria across the SCV membrane and are targeted to Salmonella-induced filaments (Sifs), tubular structures that are formed from the aggregation of host cell endosomal compartments. PipB2 is additionally targeted to vesicles that accumulate at the host cell periphery and are positive for markers of late endosomes. Both effectors are enriched in lipid rafts in host cell membranes, regions that act as important signaling platforms. PipB2, reorganizes LE/Lys compartments in mammalian cells. This activity results in the centrifugal extension of lysosomal glycoprotein (lgp)-rich membrane tubules, or Sifs, away from the SCV along microtubules. Salmonella overexpressing PipB2 induce the peripheral accumulation of LE/Lys compartments, reducing the frequency of LE/Lys tubulation. Furthermore, ectopic expression of pipB2 redistributes LE/Lys, but not other cellular organelles, to the cell periphery. In coexpression studies, PipB2 can overcome the effects of dominant-active Rab7 or Rab34 on LE/Lys positioning. Deletion of a C-terminal pentapeptide motif of PipB2, LFNEF, prevents its peripheral targeting and effect on organelle positioning. The PipB2 homologue, PipB, does not possess this motif or the same biological activity as PipB2. Therefore, it appears that a divergence in the biological functions of these two effectors can be accounted for by sequence divergence in their C-termini.